Project Summary/Abstract Traumatic and non-traumatic musculoskeletal disorders are responsible for substantial morbidity, pain and disability, affecting athletes, soldiers, active working people and elder population. This implies major social and economic hurdles, as musculoskeletal injuries represent a cost of $30 billion in U.S. each year. After injury, different therapeutic approaches are currently used in the clinics, including surgical application of autologous or allogeneic grafts. Nevertheless, complications are often associated to surgical repair including nerve injury, infection, scarring, limitations of tissue graft supply, concerns with immunological response and poor healing capacity of injured tissue. Indeed, natural healing and surgical procedures are inefficient in restoring functionality of injured muscles, resulting in a poor quality of life. Thus, a new paradigm for the treatment of musculoskeletal tissue damage is needed that can provide an effective, and long-term therapy for most patients. Here, we plan to engineer nanofibrous scaffolds with biomimetic mechanical properties that control- releases angiogenic and myogenic factors eluted through patient specific platelet-rich plasma (PRP). The nanofibrous scaffolds will be coated with a layer of hydrogel containing culture of induced pluripotent stem cells derived myogenic precursor cells (iPS-MPCs), which are expected to differentiate into highly organized myotubes. The accomplishment of the aims of this proposal will be a paradigm shift in engineering muscle tissues towards their use in treating muscular disorders and provides an effective and long-term therapy for most patients.